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Gallstone disease remains one of the most common medical problems leading to surgical intervention. Every year, approximately 500,000 cholecystectomies are performed in the US. Cholelithiasis affects approximately 10% of the adult population in the United States. It has been well demonstrated that the presence of gallstones increases with age. An estimated 20% of adults over 40 years of age and 30% of those over age 70 have biliary calculi. During the reproductive years, the female-to-male ratio is about 4:1, with the sex discrepancy narrowing in the older population to near equality. The risk factors predisposing to gallstone formation include obesity, diabetes mellitus, estrogen and pregnancy, hemolytic diseases, and cirrhosis. A study of the natural history of cholelithiasis demonstrates that approximately 35% of patients initially diagnosed with having, but not treated for, gallstones later developed complications or recurrent symptoms leading to cholecystectomy. During the last two decades, the general principles of gallstone management have not notably changed. However, methods of treatment have been dramatically altered. Today, laparoscopic cholecystectomy, laparoscopic common bile duct exploration, and endoscopic retrograde management of common bile duct (CBD) stones play important roles in the treatment of gallstones. These technological advances in the management of biliary tract disease are not infrequently accomplished by a multidisciplinary team of physicians, including surgeons trained in laparoscopic techniques, interventional gastroenterologists, and interventional radiologists. With the evolution of laparoscopic cholecystectomy, there has been a global reeducation and retraining program of surgeons. However, the treatment of choice for gallstones remains cholecystectomy. In recognition of the revolutionary advances in the treatment of cholelithiasis, it is the purpose of this collective review to describe recent information on the following topics: types of gallstones, asymptomatic gallstones, symptomatic gallstones, chronic cholecystitis, acute cholecystitis, and other complications of gallstones. Gross and compositional analysis of gallstones allows them to be classified as cholesterol, mixed, and pigment gallstones. When asymptomatic gallstones are detected during the evaluation of a patient, a prophylactic cholecystectomy is normally not indicated because of several factors. Only about 30% of patients with asymptomatic cholelithiasis will warrant surgery during their lifetime, suggesting that cholelithiasis can be a relatively benign condition in some people. However, there are certain factors that predict a more serious course in patients with asymptomatic gallstones and warrant a prophylactic cholecystectomy when they are present. These factors include patients with large (>2.5 cm) gallstones, patients with congenital hemolytic anemia or nonfunctioning gallbladders, or during bariatric surgery or colectomy. Epigastric and right upper quadrant pain occurring 30-60 minutes after meals is frequently associated with gallstone disease. The diagnosis of chronic cholecystitis is made by the presence of biliary colic with evidence of gallstones on an imaging study. Ultrasonography is the diagnostic test of choice, being 90-95% sensitive. The surgical literature suggests that 3-10% of patients undergoing cholecystectomy will have CBD stones. Intraoperative laparoscopic ultrasonography has recently replaced cholangiography as the method of choice for detecting CBD stones. Ultrasonography and radionuclide cholescintigraphy (HIDA scan) are useful in establishing a diagnosis of acute cholecystitis. Laparoscopic cholecystectomy should also be used in the treatment of acute cholecystitis. Laparoscopic cholecystectomy is more likely to be successful when performed within 3 days of the onset of symptoms. It is important to remember that gallstones can lead to a variety of other complications including choledocholithiasis, gallstone ileus, and acute gallstone pancreatitis.
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PMID:Cholelithiasis and cholecystitis. 1602 43

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20

In the recent era, use of various nutritional supplements is highly encouraged amongst the people of United States. Weight loss supplements are major part of the nutritional supplements and their usage is unregulated in the US. Obesity is a major health concern in the US and Americans spend around $30 billion a year for weight loss supplements. At times, these supplements can be responsible for documented or undocumented adverse drug effects. The health consequences related to these supplements are often overlooked by the general public, even though FDA issues advisories regarding them. One common supplement used for weight loss was Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada). Hydroxycut was recalled from the market after a FDA warning in May 2009 because of 23 reports of serious health problems ranging from jaundice and elevated liver enzymes to liver damage. 1 This case report adds evidence for Hydroxycut - induced hepatotoxicity. A 27 year old man with right upper quadrant pain and jaundice was found to have elevated liver enzymes and was taking Hydroxycut along with other supplements. Liver biopsy showed drug induced hepatotoxicity. Discontinuation of Hydroxycut dramatically improved liver functions and related symptoms.
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PMID:Hydroxycut-induced Liver Toxicity. 2466 49

Cholelithiasis affects approximately 15% of the US population. Rising trends in obesity and metabolic syndrome have contributed to an increase in diagnosis of cholelithiasis. There are several risk factors for cholelithiasis, both modifiable and nonmodifiable. Women are more likely to experience cholelithiasis than are men. Pregnancy, increasing parity, and obesity during pregnancy further increase the risk that a woman will develop cholelithiasis. The classic presentation of persons experiencing cholelithiasis, specifically when gallstones obstruct the common bile duct, is right upper quadrant pain of the abdomen that is often elicited upon palpation during physical examination and documented as a positive Murphy's sign. Referred pain to the right supraclavicular region and/or shoulder, nausea, and vomiting are also frequently reported by persons with cholelithiasis. Cholelithiasis can result in complications, including cholecystitis (inflammation of the gallbladder) and cholangitis (inflammation of the bile duct). Lack of physical examination findings does not rule out a diagnosis of cholelithiasis. Laboratory tests such as white blood cell count, liver enzymes, amylase, and lipase may assist the clinician in diagnosing cholelithiasis; however, ultrasonography is the gold standard for diagnosis. Management is dependent on severity and frequency of symptoms. Lifestyle and dietary modifications combined with medication management, such as use of gallstone dissolution agents, may be recommended for persons who have a single symptomatic episode. If symptoms become severe and/or are recurrent, laparoscopic cholecystectomy is recommended. It is recommended that individuals with an established diagnosis of cholelithiasis be referred to a surgeon and/or gastroenterologist within 2 weeks of initial presentation regardless of severity or frequency of symptoms.
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PMID:Cholelithiasis: Presentation and Management. 3090 5